PPGL tumors are rare, with an estimated annual incidence of 2 to 8 cases per million people worldwide. Approximately 80-85% of the tumors are adrenal-based pheochromocytomas and 15-20% are extra-adrenal paragangliomas. About 30-40% of cases are associated with genetic mutations in genes such as SDHB, SDHD, RET, VHL and NF1. PPGLs are most often diagnosed between ages 30-50, though hereditary cases can occur earlier.

Underlying genetic mutations are associated with some PPGL types and their location. Adrenal tumors may be associated with VHL, RET and NEF1 mutations, whereas SDHB mutations can be associated with extra-adrenal tumors in the abdomen or thorax, and SDHD mutations associated with head and neck tumors. Most PPGL cases occur sporadically from newly acquired mutations rather than from inherited mutations. No environmental, dietary or lifestyle risk factors are currently known.

PPGL symptoms are due to excessive catecholamine secretion and may be continuous or episodic. They may include:

• High blood pressure (hypertension), often resistant to treatment.

• Severe headaches.

• Sweating and palpitations (rapid heart rate).

• Anxiety or panic attack–like symptoms.

• Tremors, pallor (pale skin) or flushing.

• Abdominal pain from tumor mass (more common in extra-adrenal tumors).​

• Weight loss.

In non-functioning paragangliomas (those that do not secrete hormones), symptoms may result from compression of nearby structures.

PPGL diagnosis involves biochemical testing, imaging and genetic testing.

• Biochemical tests include measurements of plasma metanephrines or fractionated urinary metanephrines, metabolites derived from catecholamine breakdown.

• Diagnostic imaging using CT or MRI of the abdomen and pelvis can localize adrenal or extra-adrenal tumors.

Genetic testing may include screening patients for SDHB, SDHD, VHL, RET and NEF1 mutations which may appear in as many as 40% of patients. These genes are linked to mitochondrial function through tricarboxylic cycle and oxygen sensing metabolic pathways or growth factor kinase signaling pathways.

Treatment depends on the type, location, and extent of the tumor:

1. Surgical removal is the primary treatment for both pheochromocytoma and paraganglioma. Preoperative treatment with alpha-blockers to control blood pressure, and beta-blockers to control heart rate can be administered to prevent complications.​

2. For inoperable or metastatic disease, medications such as metyrosine can reduce catecholamine production, and radiation or chemotherapy may be used.

3. Lifelong follow-up is recommended to monitor for recurrence or metastasis years later.

For localized PPGLs, the tumors are benign and survival rates beyond five years can be 80-90%. However, 10-20% of tumors can behave malignantly, depending on size, location and genetic background, with SDHB mutations linked to a higher risk. With proper treatment and monitoring, most patients have excellent long-term survival.

1. Lima JV Júnior, Kater CE. 2023. “The Pheochromocytoma/Paraganglioma syndrome: an overview on mechanisms, diagnosis and management.” Int Braz J Urol. 49(3):307-319. doi: 10.1590/S1677-5538.IBJU.2023.0038. PMID: 37115176; PMCID: PMC10335895.

2. National Cancer Institute:  Pheochromocytoma and Paraganglioma.

3. Orphanet:  Pheochromocytoma-Paraganglioma.

4. Jacques W. M. Lenders, Quan-Yang Duh, Graeme Eisenhofer, Anne-Paule Gimenez-Roqueplo, Stefan K. G. Grebe, Mohammad Hassan Murad, Mitsuhide Naruse, Karel Pacak, William F. Young. 2014. “Pheochromocytoma and Paraganglioma: An Endocrine Society Clinical Practice Guideline.” The Journal of Clinical Endocrinology & Metabolism. 99(6): 1915–1942. https://doi.org/10.1210/jc.2014-1498.